Rethinking protocolized completion angiography following extremity vascular trauma: A prospective observational multicenter trial.

BACKGROUND: Completion angiography (CA) is commonly used following repair of extremity vascular injury and is recommended by the Eastern Association for the Surgery of Trauma practice management guidelines for extremity trauma. However, it remains unclear which patients benefit from CA because only level 3 evidence exists. METHODS: This prospective observational multicenter (18LI, 2LII) analysis included patients 15 years or older with extremity vascular injuries requiring operative management. Clinical variables and outcomes were analyzed with respect to with our primary study endpoint, which is need for secondary vascular intervention. RESULTS: Of 438 patients, 296 patients required arterial repair, and 90 patients (30.4%) underwent CA following arterial repair. Institutional protocol (70.9%) was cited as the most common reason to perform CA compared with concern for inadequate repair (29.1%). No patients required a redo extremity vascular surgery if a CA was performed per institutional protocol; however, 26.7% required redo vascular surgery if the CA was performed because of a concern for inadequate repair. No differences were observed in hospital mortality, length of stay, extremity ischemia, or need for amputation between those who did and did not undergo CA. CONCLUSION: Completion angiogram following major extremity injury should be considered in a case-by-case basis. Limiting completion angiograms to those patients with concern for an inadequate vascular repair may limit unnecessary surgery and morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Decreased hospital length of stay and intensive care unit admissions for non-COVID blunt trauma patients during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic overwhelmed hospitals, forcing adjustments including discharging patients earlier and limiting intensive care unit (ICU) utilization. This study aimed to evaluate ICU admissions and length of stay (LOS) for blunt trauma patients (BTPs). METHODS: A retrospective review of COVID (3/19/20-6/30/20) versus pre-COVID (3/19/19-6/30/19) BTPs at eleven trauma centers was performed. Multivariable analysis was used to identify risk factors for ICU admission. RESULTS: 12,744 BTPs were included (6942 pre-COVID vs. 5802 COVID). The COVID cohort had decreased mean LOS (3.9 vs. 4.4 days, p = 0.029), ICU LOS (0.9 vs. 1.1 days, p < 0.001), and rate of ICU admission (22.3% vs. 24.9%, p = 0.001) with no increase in complications or mortality compared to the pre-COVID cohort (all p > 0.05). On multivariable analysis, the COVID period was associated with decreased risk of ICU admission (OR = 0.82, CI 0.75-0.90, p < 0.001). CONCLUSIONS: BTPs had decreased LOS and associated risk of ICU admission during COVID, with no corresponding increase in complications or mortality.

Effects of the COVID-19 pandemic on pediatric trauma in Southern California.

PURPOSE: The COVID-19 pandemic resulted in increased penetrating trauma and decreased length of stay (LOS) amongst the adult trauma population, findings important for resource allocation. Studies regarding the pediatric trauma population are sparse and mostly single-center. This multicenter study examined pediatric trauma patients, hypothesizing increased penetrating trauma and decreased LOS after the 3/19/2020 stay-at-home (SAH) orders. METHODS: A multicenter retrospective analysis of trauma patients ≤ 17 years old presenting to 11 centers in California was performed. Demographic data, injury characteristics, and outcomes were collected. Patients were divided into three groups based on injury date: 3/19/2019-6/30/2019 (CONTROL), 1/1/2020-3/18/2020 (PRE), 3/19/2020-6/30/2020 (POST). POST was compared to PRE and CONTROL in separate analyses. RESULTS: 1677 patients were identified across all time periods (CONTROL: 631, PRE: 479, POST: 567). POST penetrating trauma rates were not significantly different compared to both PRE (11.3 vs. 9.0%, p = 0.219) and CONTROL (11.3 vs. 8.2%, p = 0.075), respectively. POST had a shorter mean LOS compared to PRE (2.4 vs. 3.3 days, p = 0.002) and CONTROL (2.4 vs. 3.4 days, p = 0.002). POST was also not significantly different than either group regarding intensive care unit (ICU) LOS, ventilator days, and mortality (all p > 0.05). CONCLUSIONS: This multicenter retrospective study demonstrated no difference in penetrating trauma rates among pediatric patients after SAH orders but did identify a shorter LOS.

COVID-19 in trauma: a propensity-matched analysis of COVID and non-COVID trauma patients.

PURPOSE: There is mounting evidence that surgical patients with COVID-19 have higher morbidity and mortality than patients without COVID-19. Infection is prevalent amongst the trauma population, but any effect of COVID-19 on trauma patients is unknown. We aimed to evaluate the effect of COVID-19 on a trauma population, hypothesizing increased mortality and pulmonary complications for COVID-19-positive (COVID) trauma patients compared to propensity-matched COVID-19-negative (non-COVID) patients. METHODS: A retrospective analysis of trauma patients presenting to 11 Level-I and II trauma centers in California between 1/1/2019-6/30/2019 and 1/1/2020-6/30/2020 was performed. A 1:2 propensity score model was used to match COVID to non-COVID trauma patients using age, blunt/penetrating mechanism, injury severity score, Glasgow Coma Scale score, systolic blood pressure, respiratory rate, and heart rate. Outcomes were compared between the two groups. RESULTS: A total of 20,448 trauma patients were identified during the study period. 53 COVID trauma patients were matched with 106 non-COVID trauma patients. COVID patients had higher rates of mortality (9.4% vs 1.9%, p = 0.029) and pneumonia (7.5% vs. 0.0%, p = 0.011), as well as a longer mean length of stay (LOS) (7.47 vs 3.28 days, p < 0.001) and intensive care unit LOS (1.40 vs 0.80 days, p = 0.008), compared to non-COVID patients. CONCLUSION: This multicenter retrospective study found increased rates of mortality and pneumonia, as well as a longer LOS, for COVID trauma patients compared to a propensity-matched cohort of non-COVID patients. Further studies are warranted to validate these findings and to elucidate the underlying pathways responsible for higher mortality in COVID trauma patients.

The coronavirus disease 2019 (COVID-19) stay-at-home order's unequal effects on trauma volume by insurance status in Southern California.

BACKGROUND: The rapid spread of coronavirus disease 2019 in the United States led to a variety of mandates intended to decrease population movement and "flatten the curve." However, there is evidence some are not able to stay-at-home due to certain disadvantages, thus remaining exposed to both coronavirus disease 2019 and trauma. We therefore sought to identify any unequal effects of the California stay-at-home orders between races and insurance statuses in a multicenter study utilizing trauma volume data. METHODS: A posthoc multicenter retrospective analysis of trauma patients presenting to 11 centers in Southern California between the dates of January 1, 2020, and June 30, 2020, and January 1, 2019, and June 30, 2019, was performed. The number of trauma patients of each race/insurance status was tabulated per day. We then calculated the changes in trauma volume related to stay-at-home orders for each race/insurance status and compared the magnitude of these changes using statistical resampling. RESULTS: Compared to baseline, there was a 40.1% drop in total trauma volume, which occurred 20 days after stay-at-home orders. During stay-at-home orders, the average daily trauma volume of patients with Medicaid increased by 13.7 ± 5.3%, whereas the volume of those with Medicare, private insurance, and no insurance decreased. The average daily trauma volume decreased for White, Black, Asian, and Latino patients with the volume of Black and Latino patients dropping to a similar degree compared to White patients. CONCLUSION: This retrospective multicenter study demonstrated that patients with Medicaid had a paradoxical increase in trauma volume during stay-at-home orders, suggesting that the most impoverished groups remain disproportionately exposed to trauma during a pandemic, further exacerbating existing health disparities.

Changes in traumatic mechanisms of injury in Southern California related to COVID-19: Penetrating trauma as a second pandemic.

BACKGROUND: The COVID-19 pandemic resulted in a statewide stay-at-home (SAH) order in California beginning March 19, 2020, forcing large-scale behavioral changes and taking an emotional and economic toll. The effects of SAH orders on the trauma population remain unknown. We hypothesized an increase in rates of penetrating trauma, gunshot wounds, suicide attempts, and domestic violence in the Southern California trauma population after the SAH order. METHODS: A multicenter retrospective analysis of all trauma patients presenting to 11 American College of Surgeons levels I and II trauma centers spanning seven counties in California was performed. Demographic data, injury characteristics, clinical data, and outcomes were collected. Patients were divided into three groups based on injury date: before SAH from January 1, 2020, to March 18, 2020 (PRE), after SAH from March 19, 2020, to June 30, 2020 (POST), and a historical control from March 19, 2019, to June 30, 2019 (CONTROL). POST was compared with both PRE and CONTROL in two separate analyses. RESULTS: Across all periods, 20,448 trauma patients were identified (CONTROL, 7,707; PRE, 6,022; POST, 6,719). POST had a significantly increased rate of penetrating trauma (13.0% vs. 10.3%, p < 0.001 and 13.0% vs. 9.9%, p < 0.001) and gunshot wounds (4.5% vs. 2.4%, p = 0.002 and 4.5% vs. 3.7%, p = 0.025) compared with PRE and CONTROL, respectively. POST had a suicide attempt rate of 1.9% and a domestic violence rate of 0.7%, which were similar to PRE (p = 0.478, p = 0.514) and CONTROL (p = 0.160, p = 0.618). CONCLUSION: This multicenter Southern California study demonstrated an increased rate of penetrating trauma and gunshot wounds after the COVID-19 SAH orders but no difference in attempted suicide or domestic violence rates. These findings may provide useful information regarding resource utilization and a target for societal intervention during the current or future pandemic(s). LEVEL OF EVIDENCE: Epidemiological, level IV.

hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice.

Seizure disorders debilitate more than 65,000,000 people worldwide, with temporal lobe epilepsy (TLE) being the most common form. Previous studies have shown that transplantation of GABA-releasing cells results in suppression of seizures in epileptic mice. Derivation of interneurons from human pluripotent stem cells (hPSCs) has been reported, pointing to clinical translation of quality-controlled human cell sources that can enhance inhibitory drive and restore host circuitry. In this study, we demonstrate that hPSC-derived maturing GABAergic interneurons (mGINs) migrate extensively and integrate into dysfunctional circuitry of the epileptic mouse brain. Using optogenetic approaches, we find that grafted mGINs generate inhibitory postsynaptic responses in host hippocampal neurons. Importantly, even before acquiring full electrophysiological maturation, grafted neurons were capable of suppressing seizures and ameliorating behavioral abnormalities such as cognitive deficits, aggressiveness, and hyperactivity. These results provide support for the potential of hPSC-derived mGIN for restorative cell therapy for epilepsy.

Stem cell grafting improves both motor and cognitive impairments in a genetic model of Parkinson's disease, the aphakia (ak) mouse.

Stem cell-based cell replacement of lost midbrain dopamine (mDA) neurons is a potential therapy for Parkinson's disease (PD). Toward this goal, it is critical to optimize various aspects of cell transplantation and to assess functional recovery through behavioral tests in validated animal model(s) of PD. At present, cell transplantation studies are being done almost exclusively in neurotoxin-based animal models, because few genetic models of PD exhibit robust mDA neuronal loss. Here we used a genetic model of PD, the aphakia mouse, which demonstrates selective degeneration of mDA neurons in the substantia nigra. We systematically investigated the functional effects of transplanting embryonic stem cell-derived cells at different stages of in vitro differentiation: embryoid body (EB), neural progenitor (NP), and neuronal differentiated (ND) stages. We found that transplantation of NP cells yielded the best outcomes for both survival and behavioral improvement, while transplantation of EB and ND cells resulted in high teratoma-like tumor formation and poor survival, respectively. In behavioral paradigms specific to basal ganglia, the NP cells group prominently improved motor behavioral defects 1 and 2 months posttransplantation. Furthermore, we found that NP cell transplantation also improved cognitive impairments of aphakia mice, as examined by the passive avoidance task. Importantly, these graft-induced functional improvements well correlated with survival of tyrosine hydroxylase-positive DA neurons. Taken together, we propose that the aphakia mouse can serve as a novel and useful platform for cell transplantation studies to assess both neurological and cognitive improvements and that NP stage cells represent an optimal stage for transplantation.

ES cell-derived renewable and functional midbrain dopaminergic progenitors.

During early development, midbrain dopaminergic (mDA) neuronal progenitors (NPs) arise from the ventral mesencephalic area by the combined actions of secreted factors and their downstream transcription factors. These mDA NPs proliferate, migrate to their final destinations, and develop into mature mDA neurons in the substantia nigra and the ventral tegmental area. Here, we show that such authentic mDA NPs can be efficiently isolated from differentiated ES cells (ESCs) using a FACS method combining two markers, Otx2 and Corin. Purified Otx2(+)Corin(+) cells coexpressed other mDA NP markers, including FoxA2, Lmx1b, and Glast. Using optimized culture conditions, these mDA NPs continuously proliferated up to 4 wk with almost 1,000-fold expansion without significant changes in their phenotype. Furthermore, upon differentiation, Otx2(+)Corin(+) cells efficiently generated mDA neurons, as evidenced by coexpression of mDA neuronal markers (e.g., TH, Pitx3, Nurr1, and Lmx1b) and physiological functions (e.g., efficient DA secretion and uptake). Notably, these mDA NPs differentiated into a relatively homogenous DA population with few serotonergic neurons. When transplanted into PD model animals, aphakia mice, and 6-OHDA-lesioned rats, mDA NPs differentiated into mDA neurons in vivo and generated well-integrated DA grafts, resulting in significant improvement in motor dysfunctions without tumor formation. Furthermore, grafted Otx2(+)Corin(+) cells exhibited significant migratory function in the host striatum, reaching >3.3 mm length in the entire striatum. We propose that functional and expandable mDA NPs can be efficiently isolated by this unique strategy and will serve as useful tools in regenerative medicine, bioassay, and drug screening.

Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway.

Selective degeneration of midbrain dopaminergic (mDA) neurons is associated with Parkinson's disease (PD), and thus an in-depth understanding of molecular pathways underlying mDA development will be crucial for optimal bioassays and cell replacement therapy for PD. In this study, we identified a novel Wnt1-Lmx1a autoregulatory loop during mDA differentiation of ESCs and confirmed its in vivo presence during embryonic development. We found that the Wnt1-Lmx1a autoregulatory loop directly regulates Otx2 through the beta-catenin complex and Nurr1 and Pitx3 through Lmx1a. We also found that Lmx1a and Lmx1b cooperatively regulate mDA differentiation with overlapping and cross-regulatory functions. Furthermore, coactivation of both Wnt1 and SHH pathways by exogenous expression of Lmx1a, Otx2, and FoxA2 synergistically enhanced the differentiation of ESCs to mDA neurons. Together with previous works, this study shows that two regulatory loops (Wnt1-Lmx1a and SHH-FoxA2) critically link extrinsic signals to cell-intrinsic factors and cooperatively regulate mDA neuron development.

Assessing quality of life of patients with advanced chronic obstructive pulmonary disease in the end of life.

Given the limitations of existing health-related quality-of-life (QOL) measures in capturing the end-of-life experience of patients with advanced chronic diseases, an empirically grounded instrument, the quality-of-life concerns in the end of life questionnaire (QOLC-E), was developed. Though it was built on the McGill quality of life questionnaire (MQOL), its sphere is more holistic and culturally specific for the Chinese patients in Hong Kong. One hundred and forty-nine patients with advanced chronic obstructive pulmonary disease (COPD) or metastatic cancer completed the questionnaire. Seven factors (28 items) which emerged from the factor analysis were grouped into four positive (support, value of life, food-related concerns, and healthcare concerns) and four negative (physical discomfort, negative emotions, sense of alienation, and existential distress) subscales. Good internal consistency and concurrent validity were shown. The results also revealed that these two groups of patients had similar QOL concerns. The validity of applying QOLC-E as an outcome measure to evaluate the effectiveness of palliative and psychoexistential interventions has yet to be tested.